Temporal trends in colorectal cancer mortality rates (1999–2022) in the United States

Abstract Colorectal cancer (CRC) ranks as the third leading cause of cancer‐related deaths in the United States (U.S.). Our study aims to analyze CRC mortality patterns in the U.S., focusing on gender and age groups from 1999 to 2022. We analyzed Age‐Adjusted Mortality Rates (AAMRs) for CRC‐related deaths using the CDC Wide‐ranging Online Data for Epidemiologic Research (CDC WONDER) database and assessed differences between age and sex. CRC‐related mortality decreased significantly from 1999 to 2011 (−2.81% APC) and from 2011 to 2020 (−1.95% APC) but a not significant uptrend from 2020 to 2022 (2% APC). Males experienced a more significant decrease. Among age groups, crude mortality decreased until 2020, except in age group 45–54, which showed an annual increase in mortality of 0.9% from 2004 to 2022. Furthermore, individuals aged 75–84 and 85+ saw a nonsignificant annual increase of 1.8% and 4.5% from 2020 to 2022, respectively. Our study highlights a significant decline in age and gender‐specific CRC‐related mortality from 1999 to 2020. However, the worrisome uptrend observed in the younger age group of 45–54 emphasizes the importance of implementing targeted public health measures and evidence‐based interventions.

ranging Online Data for Epidemiologic Research (CDC WONDER) database and assessed differences between age and sex.CRC-related mortality decreased significantly from 1999 to 2011 (À2.81%APC) and from 2011 to 2020 (À1.95% APC) but a not significant uptrend from 2020 to 2022 (2% APC).Males experienced a more significant decrease.Among age groups, crude mortality decreased until 2020, except in age group 45-54, which showed an annual increase in mortality of 0.9% from 2004 to 2022.Furthermore, individuals aged 75-84 and 85+ saw a nonsignificant annual increase of 1.8% and 4.5% from 2020 to 2022, respectively.Our study highlights a significant decline in age and gender-specific CRC-related mortality from 1999 to 2020.However, the worrisome uptrend observed in the younger age group of 45-54 emphasizes the importance of implementing targeted public health measures and evidence-based interventions.

| INTRODUCTION
2][3] The prevalence of CRC burden exhibits substantial variability, with over two-thirds of total cases and approximately 60% of all related deaths concentrated in nations characterized by a high or very high human development index. 3Various environmental and genetic factors, including lifestyle, dietary habits, family history, and metabolic health conditions, contribute to CRC risk. 4Despite progress in early detection and therapeutic measures, colorectal cancer (CRC) persists as the third most common cause of cancer-related deaths in the United States. 1 It is imperative to monitor CRC mortality trends to evaluate existing interventions effectively and pinpoint areas for improvement. 1,2Moreover, the recent surge in early-onset colorectal cancer, coupled with the subsequent revision of the recommended screening protocol by the US Preventive Service Task Force (USPSTF), emphasizes the crucial role of routine screening for individuals aged 45-75 years. 2 This study aims to scrutinize and discuss trends in CRC-related mortality rates among individuals aged 35 and above in the United States from 1999 to 2022.
The nuanced analysis of mortality trends offers valuable insights into the overall impact of preventive methods, such as screening protocols and advancements in treatment, allowing us to gauge the effectiveness of the multifaceted strategies employed in addressing this significant public health challenge.By conducting this analysis, the research aims to provide valuable insights into the effectiveness of current strategies, identify potential avenues for enhancing interventions, and ultimately inform public health initiatives geared toward reducing the burden of colorectal cancer and improving patient outcomes.

| Study population
Data obtained from the Centers for Disease Control and Prevention (CDC), were used to analyze colorectal cancer related mortality rates per 100 000 population from 1999 through 2022.CRC patients were identified using ICD-10 diagnostic codes C18-C19.Additional demographic information is not provided in CDC wonder database to protect patient privacy. 3l patients with ages 35 years or above were included in our study. 3We excluded patients under the age of 35 due to their lower mortality rates, as including them could introduce confounding factors and because they did not fall within our population of interest.

| Statistical analysis
Age-adjusted mortality rates (AAMRs) were utilized for the study and standardized to the 2000 U.S. population.For age subgroups, crude mortality rates (CMR) were analyzed.Trends were established using the Joinpoint Trend Analysis Software (version 5.0.1), which assesses temporal trends in the Average Percentage Change (APC).The analysis with Joinpoint involved a Monte Carlo permutation test and a ttest to accurately detect "joinpoints"-the points at which there is a statistically significant change in the trend. 4This combination allows for the detection of both gradual and abrupt trend changes over time.
Additionally, we included log-linear regression models in our analysis to provide a more comprehensive understanding of the trends in agestandardized mortality rates.This regression modeling approach was vital for understanding the direction and strength of these trends. 4ends were regarded as increasing or decreasing when the APC significantly differed from 0 (p < .05)using a two-sided test.
Two joinpoints were identified, with a significant decline, as shown in Figure 2.
In age-stratified analyses, crude mortality trends have been steadily decreasing for all age groups until 2020, except in age group 45-54, which showed an increase in mortality by 0.9% (95% CI, 0.66%-1.15%)annually from 2004 to 2020 (Figure 1).All additional age subgroups showed a significant decline in mortality for the study period, with variable joint points identified, as shown in Figure 1.

| DISCUSSION
Our examination of colorectal cancer (CRC)-related mortality trends from 1999 to 2022 revealed a substantial decline in mortality rates from 1999 to 2022, but a nonsignificant uptick from 2020 to 2022.
The decrease until 2020 is attributed to significant advancements in early detection and prevention, instrumental in reducing CRC incidence and mortality rates. 5Recognizing the importance of organized screening programs, we advocate for diverse screening methods such as sigmoidoscopy, guaiac-based fecal occult-blood testing (FOBT), colonoscopy, and fecal immunochemical tests (FIT). 6,7We propose an inclusive strategy by emphasizing integrating fecal testing alongside colonoscopies to enhance screening rates and accommodate patient preferences. 8raveling the pathophysiology of CRC has significantly contributed to the decline in mortality rates, offering diverse treatment options, including endoscopic and surgical excision, immunotherapy, radiotherapy, targeted therapy, and minimally invasive procedures. 9though effective, these treatments have notably doubled overall survival for advanced disease to 3 years, while individuals with nonmetastasized disease continue to experience favorable outcomes.
However, the significant increase in mortality in the age group of 45-54 from 2004 to 2022 may be linked to rising incidence rates, especially in early-onset CRC. 10 Recent recommendations for screening starting at age 45 acknowledge this trend, but its impact on disease burden remains uncertain.Our findings emphasize the need for interventions to enhance screening participation in the 45-54 age group, considering the surge in CRC incidence and low on-time screening rates at age 50. 11The rise in stool testing adoption among underserved communities is seen as a potential solution to improve screening rates, particularly during healthcare disruptions like the COVID-19 pandemic.The birth cohort effect since the 1950s may also contribute to the observed mortality increase, emphasizing the urgency of identifying factors and implementing targeted interventions for this age group.
Our study also unveiled a nonsignificant increase in mortality rates from 2020 to 2022, impacting both genders disparately and notably affecting individuals aged 75-84 and those aged 85 and older.This surge could be partly attributed to the national emergency declaration in response to the COVID-19 pandemic, resulting in an 80%-85% decline in CRC screening volume. 12,13Timely screening, essential for improved prognosis and reduced cases and deaths, faced challenges during the pandemic.A study by Worthington et al. underscored the global impact of COVID-19 disruptions on organized colorectal cancer screening, indicating potential additional CRC cases and deaths globally from 2020 to 2050. 14derly patients, constituting one-third of new CRC diagnoses globally, face unique challenges with inadequate treatment, contributing to poor adherence and suboptimal treatment quality. 15me-to-treatment initiation delays during the pandemic significantly elevated mortality risk. 14The unexpected rise in mortality during the pandemic emphasizes the critical need for ongoing monitoring and targeted health interventions, particularly for older populations.
Our study's strengths include its broad scope and diverse data sources, enhancing its potential generalizability.Spanning 23 years and using the CDC's online epidemiologic database, it offers a thorough of colorectal cancer (CRC) mortality trends, including during the COVID-19 peak.This period, from 1999 to 2022, highlights the impact of COVID-related screening declines, underlining the need for timely CRC screening.However, the study has limitations.Relying on ICD codes and death certificates may lead to underrepresented CRC mortality.Inaccuracies in reporting, especially regarding race and ethnicity, could skew results and hinder our ability to address mortality disparities.The inclusion of the COVID-19 period adds complexity.These factors suggest caution in interpreting our findings and call for further research to improve CRC data accuracy.AUTHOR CONTRIBUTIONS Fariha Ilyas: Conceptualization (equal); data curation (equal); writingoriginal draft (equal); writingreview and editing (equal).Eiman Ahmed: Supervision (equal); validation (equal); visualization (equal).Hassam Ali: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); project administration (equal).Maheen Ilyas: Software (equal); supervision (equal); validation (equal); writingoriginal draft (equal); writingreview and editing (equal).Shiza Sarfraz: Methodology (equal); project administration (equal); writingoriginal draft (equal); writingreview and editing (equal).Mahnoor Khalid: Data curation (equal); formal analysis (equal); resources (equal).Muhammad Khalaf: Software (equal);

F I G U R E 1
Trends in colorectal cancer mortality from 1999 to 2022 in the United States, stratified by age groups.Total rates are reported as age adjusted mortality rate, age groups are reported as crude mortality rates.F I G U R E 2 Trends in Colorectal Cancer Mortality from 1999 to 2022 in the United States, stratified by gender.writingoriginaldraft (equal); writingreview and editing (equal).Prashant Reddy Mudireddy: Supervision (equal); writingoriginal draft (equal); writingreview and editing (equal).